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Increased tumorigenicity of human keratinocytes harboring human papillomavirus type 16 is associated with resistance to endogenous tumor necrosis factor‐α‐mediated growth limitation
Author(s) -
Malejczyk Jacek,
Malejczyk Magdalena,
Majewski Slawomir,
Breitburd Françoise,
Luger Thomas A.,
Jablonska Stefania,
Orth Gerard
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910560421
Subject(s) - autocrine signalling , tumor necrosis factor alpha , cytokine , biology , cell culture , cell growth , in vitro , microbiology and biotechnology , cancer research , growth factor , receptor , immunology , endocrinology , biochemistry , genetics
The aim of this study was to evaluate the relationship between tumorigenicity of cell sublines derived from weakly tumorigenic SKv‐e and SKv‐I keratinocytes harboring human papillomavirus type 16 (HPV 16) and their susceptibility to autocrine growth limitation mediated by tumor necrosis factor‐α (TNF‐α). These sublines displayed different in vitro proliferative potential which correlated with tumorigenicity in nu / nu mice. Recombinant TNF‐α inhibited in vitro growth of weakly tumorigenic parental SKv cell lines while it did not affect proliferation of their respective highly tumorigenic sublines. Resistance to TNF‐α correlated with both increased in vitro proliferation and tumorigenicity. Anti‐TNF‐α antibodies (Ab) significantly increased in vitro proliferation of weakly tumorigenic parental SKv cells up to the levels of their highly tumorigenic sublines. Growth of highly tumorigenic SKv cells was not affected. On the other hand, proliferation of SKv cells was affected neither by transforming growth factor‐β (TGF‐β) nor by anti‐TGF‐β Ab. All SKv cell sublines tested spontaneously released TNF‐α, as evaluated by a specific radioimmunoassay; however, the levels of the endogenous cytokine were not related to their proliferative potential and tumorigenicity. An increased resistance to the anti‐proliferative effect of TNF‐α may be associated with decreased expression of TNF‐α receptors (TNF‐αR) inasmuch as evaluation of 125 I‐TNF‐α binding and Northern‐blot analysis of TNF‐αR‐specific mRNA showed that highly tumorigenic SKv cell sublines expressed significantly lower numbers of TNF‐αR than their respective parental cells. These results show that an increased tumorigenicity of HPV 16‐harboring SKv keratinocytes may be, at least partially, due to escape from autocrine TNF‐α‐mediated growth limitation.